An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression

Jungsun Kim; John P Hoffman; R Katherine Alpaugh; Andrew D Rhim; Andrew D Rhimm; Maximilian Reichert; Ben Z Stanger; Emma E Furth; Antonia R Sepulveda; Chao-Xing Yuan; Kyoung-Jae Won; Greg Donahue; Jessica Sands; Andrew A Gumbs; Kenneth S Zaret

doi:10.1016/j.celrep.2013.05.036

An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression

Jungsun Kim, John P Hoffman, R Katherine Alpaugh, Andrew D Rhim, Andrew D Rhimm, Maximilian Reichert, Ben Z Stanger, Emma E Furth, Antonia R Sepulveda, Chao-Xing Yuan, Kyoung-Jae Won, Greg Donahue, Jessica Sands, Andrew A Gumbs, Kenneth S Zaret

96 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC) lines were not of the expected cancer genotype, one PDAC line, 10-22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN) precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

Original language	English
Journal	Cell Reports
Volume	3
Issue number	6
Pages (from-to)	2088-99
Number of pages	12
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2013.05.036
Publication status	Published - 27 Mar 2013
Externally published	Yes

Keywords

Animals
Biomarkers, Tumor/genetics
Carcinoma, Pancreatic Ductal/genetics
Cattle
Cell Line, Tumor
Disease Models, Animal
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Induced Pluripotent Stem Cells/pathology
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells/pathology
Pancreatic Neoplasms/genetics
Precancerous Conditions/genetics
Prognosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2013.05.036Licence: CC BY-NC-ND

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Kim, J., Hoffman, J. P., Alpaugh, R. K., Rhim, A. D., Rhimm, A. D., Reichert, M., Stanger, B. Z., Furth, E. E., Sepulveda, A. R., Yuan, C-X., Won, K-J., Donahue, G., Sands, J., Gumbs, A. A., & Zaret, K. S. (2013). An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Reports, 3(6), 2088-99. https://doi.org/10.1016/j.celrep.2013.05.036

Kim, J, Hoffman, JP, Alpaugh, RK, Rhim, AD, Rhimm, AD, Reichert, M, Stanger, BZ, Furth, EE, Sepulveda, AR, Yuan, C-X, Won, K-J, Donahue, G, Sands, J, Gumbs, AA & Zaret, KS 2013, 'An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression', Cell Reports, vol. 3, no. 6, pp. 2088-99. https://doi.org/10.1016/j.celrep.2013.05.036

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abstract = "Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC) lines were not of the expected cancer genotype, one PDAC line, 10-22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN) precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression. ",

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AB - Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC) lines were not of the expected cancer genotype, one PDAC line, 10-22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN) precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

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An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression

Abstract

Keywords

UN SDGs

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